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Daniel Dunaief

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William Farr. Photo by Anja von der Linden

By Daniel Dunaief

It’s not exactly a symphony, with varying sounds, tones, cadences and resonances all working together to take the listener on an auditory journey through colors, moods and meaning. In fact, the total length of the distortion is so short — about 0.1 seconds — that it’s a true scratch-your-ear-and-you’ll-miss-it moment.

And yet, astrophysicists like William Farr, an associate professor in the Department of Physics and Astronomy at Stony Brook University and a group leader in gravitational wave astronomy with the Simons Foundation Flatiron Institute, are thrilled that they have been able to measure distortions in space and time that occur at audio frequencies that they can convert into sounds. These distortions were made millions or even billions of years ago from merging black holes.

Farr, in collaboration with a team of scientists from various institutions, recently published a paper in Physical Review Letters on the topic. 

While the ability to detect sounds sent hurtling through space billions of years before Tyrannosaurus Rex stalked its prey on Earth with its mammoth jaw and short forelimbs offers some excitement in and of itself, Farr and other scientists are intrigued by the implications for basic physical principles.

General relativity, a theory proposed by Albert Einstein over 100 years ago, offers specific predictions about gravitational waves traveling through space.“The big excitement is that we checked those predictions and they matched what we saw. It’s a very direct test of general relativity and its predictions about a super extreme environment near a black hole,” said Farr. There are other tests of general relativity, but none that directly test its predictions so close to the event horizon of a black hole, he explained.

General relativity predicts a spectrum of tones from a black hole, much like quantum mechanics predicts a spectrum line from a hydrogen atom, Farr explained.

The result of this analysis “provides another striking confirmation of the theory of general relativity and also demonstrates that there are even more exciting things that can be done with gravitational wave astrophysics,” Marilena Loverde, an assistant professor of physics at the C. N. Yang Institute for Theoretical Physics at Stony Brook University, explained in an email. Loverde suggested that Farr is “particularly well-known for bringing powerful new statistical techniques to extract science from vast astrophysical data sets.”

Farr and his colleagues discovered two distortions that they converted into tones from one merger event. By measuring the frequency of the first one, they could predict the frequency for all the other tones generated in the event. They detected one more event, whose frequency and decay rate were consistent with general relativity given the accuracy of the measurement.

So, what does the merger of two black holes sound like, from billions of light years away? Farr suggested it was like a “thunk” sent over that tremendous distance. The pitch of that sound varies depending on the masses of the black holes. The difference in sound is akin to the noise a bear makes compared with a chipmunk: A larger black hole, or animal, in this comparison, makes a noise with a deeper pitch.

He used data from the Laser Interferometer Gravitational-Wave Observatory, or LIGO, which is a twin system located in Livingston, Louisiana, and Hanford, Washington. LIGO had collected data from black hole merger events over a noncontinuous six-month period from 2015 to 2017.

Farr chose the loudest one, which came from 1.5 billion years ago. Farr was using data from the instrument, which collects gravitational waves as they reach the two different locations, when it was less sensitive. Given the original data, he might not have discovered anything. He was, however, delighted to discover the first tone.

If something that far away emitted a gravitational wave sound that lasts such a short period of time, how, then, could the LIGO team and Farr’s analysis be sure the sound originated with the cosmic collision?

“We make ‘extreme’ efforts to be sure about this,” Farr explained in an email. “It is one reason we built two instruments (so that something weird happening in one does not fool us).” He said he makes sure the signal is consistently recorded in both concurrently. To rule out distortions that might come from other events, like comets slamming into exoplanets, he can measure the frequency of the event and its amplitude.

Black holes form when stars collapse. After the star that, in this case, was likely around 25 times the mass of the sun, exploded, what was left behind had an enormous mass. When another, nearby star becomes a black hole, the two black holes develop an orbit like their progenitor stars. When these stars become black holes, they will emit enough gravitational waves to shrink the orbit, leading to a merger over a few billion years. That’s what he “heard” from the last second or fraction of a second.

Farr expects to have the chance to analyze considerably more data over the next few months. First, he is working to analyze data that has already been released and then he will explore data from this year’s observations, which includes about 25 more mergers.

“The detectors are getting more sensitive,” he said. This year, scientists can see about 30 percent further than they could in the first and second observing runs, which translates into seeing over twice the total volume.

Farr has been at Stony Brook for almost a year. Prior to his arrival, he had lived in England for five years. He and his wife, Rachel, who have a 3½-year-old daughter, Katherine, live in Stony Brook.

As for his work, Farr is thrilled that he will have a chance to study more of these black hole merger sounds that, while not exactly Mozart, are, nonetheless, music to his ears. “Each different event tells us different things about how stars form and evolve,” he said.

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By Daniel Dunaief

Daniel Dunaief

We are back to shopping for college. There’s a familiar rhythm to this search that, the second time through, brings a more relaxed pace. Now that my wife and I have taken about a dozen college tours, we’ve noticed patterns. Please find below some observations:

• The library gets quieter the higher its location. Every school we’ve toured has suggested that people will throw visual daggers at you on the top floor if you drop your pencil. Move to a lower floor to cough. In the effort to differentiate one school from another, a clever college ought to invert the quiet pyramid. The logistics would be challenging, with people stepping onto a floor of silence, but it would make clear how serious students were in the library and would defy the usual expectations about noise on each floor.

• Showcase dorm rooms aren’t real. Yes, the rooms everyone sees are, of course, actual rooms, but they have considerably less stuff, no irrational roommates who scream in their sleep, and are better lit than the freshmen rooms most of our kids will occupy. Somehow, the temperature in these rooms is perfect for almost everyone. Many rooms, however, are way too hot or too cold for one, two or the three people jammed into a space that will feel like the garbage chute in the original “Star Wars” as the year progresses.

• Some tour guides will share their food choices, preferences and idiosyncrasies because it makes them charming. We may not have the same aversion to Vegan Tuesdays, but we will undoubtedly remember the school because some lacrosse player in desperate need of a haircut who sings hates vegan food.

• Tour guides are friendly. Yeah, I know, shocking, right? But, while they are talking to us, many wave to friends as they speak. Are they really waving at someone? Is one person walking back and forth? The whole “everyone loves me and I love everyone” shtick seems rehearsed. Then again, maybe tour guides really do have friends everywhere.

• Some information sessions and tours seem to have left something crucial out of the discussion: Who wouldn’t be a great fit for their extraordinary school? Schools might save themselves — and prospective students — trouble if they helped these eager high school seniors and juniors get a better idea of what might not work for them. None of the schools offer an amalgamated profile of the type of student who typically transfers anywhere else. They should, right? Wouldn’t it help to know that the snow which starts in September and ends in May drives some students away? Or that the competitive atmosphere on campus doesn’t work for some students? What have the schools learned from some of their admissions mistakes?

• People on tours generally look and sound tired. Most of the kids seem to be praying that their parents don’t embarrass them by asking too many questions. When asked what they plan to major in, they respond with something like “blobology” or “Idunnonotsure.” The introductory phase of the tour rarely creates cohesion among a group taking turns to hold doors open for each other.

• Tour guides attempt to share college humor by highlighting their personal deficiencies. In between waving to their extended group of friends, these guides point to a chemistry building or a music hall and suggest that they have absolutely no skills in those fields whatsoever and are in awe of their peers, who seem to be speaking a foreign language when they explain their passion for molecular biology.

• These guides pick majors and minors like they’re at an ice cream store: They have one scoop of biology, two small scoops of elementary education and sociology, and a sprinkling of criminal justice.

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Jessica Schleider. Photo from SBU

By Daniel Dunaief

Many teenagers who are struggling with depression need help. According to several estimates, less than half of teens with depression receive treatment that would help them manage through everything from negative feelings toward themselves and their lives to a lack of control over events during the day.

Jessica Schleider, an assistant professor of clinical psychology in the College of Arts and Sciences at Stony Brook University, wants to offer teenagers battling depression a new kind of assistance.

Jessica Schleider on a hike with her dog Penny. Photo by David Payne

Schleider is seeking participants for a new study, called Project Track to Treat, that offers teenagers from 11 to 16 years old symptom-tailored treatment. After participating teens respond to surveys she sends them on smartphones, she will provide single-session, computer-based interventions that address symptoms such as hopelessness or withdrawal from daily activities.

Schleider recently received a five-year, $2 million Early Independence Award from the National Institutes of Health to test the benefits of these half-hour computer sessions.

The funds will go toward study staff, the cost of recruiting youths and families for the study, equipment, statistical packages for the analyses she plans to run and compensation for the families who take part.

“A vast majority of teenagers who experience depression never access treatment,” Schleider said, potentially because teens are not typically in a position where they can seek out treatment on their own. “Between the lack of access to services and the limited potency of services, there needs to be a broader array of options and layers we can provide.”

In the world of clinical psychology, three to four months is generally considered brief treatment. A single computer-based session that a teenager can access at any time offers support during a much shorter time frame.

The idea behind the briefer, more targeted intervention is that it could offer help. The goal of the session is to create positive momentum, to teach teens useful skills for coping with depression-related difficulties, and to offer it in a setting where modern teenagers spend much of their time, online, Schleider suggested.

Jessica Shleider with husband David Payne and their dog Penny.
Photo from Jessica Schleider

“For young people who would never go to a therapist, the question may be whether there is something else that could help, and [Schleider’s] work may offer one such ‘something else,’” John Weisz, a professor in the Department of Psychology at Harvard University, wrote in an email. It’s also possible, explained Weisz, who has known Schleider since 2013 when she worked in his lab, that a single session might encourage teenagers to believe that other types of therapy can also help if they try.

Part of the motivation for this study is to determine if the nature of the symptoms — which she will explore through survey questions — can inform how teenagers will respond to a single, therapeutic session.

Schleider created these programs from available research in psychology and education. She adapted some of those programs to these specific circumstances and she taught herself rudimentary coding with html. She currently has three programs available on her website, which interested parents and teenagers can explore at www.schleiderlab.org/participate.

The teenagers participating in the study will receive questions a few times a day for three weeks about how they are feeling, checking to see any signs of depression. From those interactions, Schleider will be able to determine which symptom is the most central and which might lead to other symptoms over time. She hopes to take parameters from that to see if those symptoms predict how much a participant will respond to a session.

Schleider will also measure how teenagers respond to training through the study. If their emotional state deteriorates, the researchers can intervene and can monitor the level of risk and refer any cases appropriately. “Our top priority as researchers is to make sure the kids are taken care of,” she said.

She was skeptical before she started working on brief sessions. “I was on the side of, of course you can’t do anything in one session,” Schleider said. “I thought you need several sessions to make a sustained change.”

In looking at the available research, however, she discovered that through 50 randomized control trials in 2017, the magnitude of the effect of the trials was between small to medium range, which matched the effect of sessions ranging from an hour to 16 sessions for other teenagers. After her study, she realized that “there is something to this. We need to do more work to find out what to do and how to harness it for our youth.”

Through monitoring over two years, Schleider hopes to gain a better awareness of who will benefit from this session and under what time frame they might see an improvement.

She hopes teenagers can share their thoughts and ideas for how to improve these programs. She also offers some of these teenagers to help reconstruct the content and language and references.

Teenagers who don’t participate in the Track to Treat study can participate in an anonymous Project Yes effort, which is a program evaluation initiative. These participants can offer feedback on these sessions.

For a subset of teenagers, one session likely won’t be sufficient. 

Weisz suggested that Schleider, who joined Stony Brook last year, is a “terrific addition” to the university and the community. “I believe her work will reflect very well on both.” Weisz added that Schleider’s colleagues in the Department of Psychology at Stony Brook “are among the finest psychological scientists in the nation,” where Schleider can “take her work to a very high level.”

Schleider, who joined Stony Brook last year, lives in Coram with her husband, David Payne, who is a medical resident in radiology at Stony Brook Hospital. 

As for her work, Schleider said she recognizes that there is no panacea, but that this approach is “something when the alternative is nothing.”

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Photo from YouTube

By Daniel Dunaief

Daniel Dunaief

Looking back at the six-game American League Championship Series, it’s clear that the Houston Astros were the better team. Tough as it is to write that when my fan allegiance is with the Yankees, the Astros had more clutch hitting, better defense, and better starting and relief pitching. Yes, the two teams were fairly evenly matched when it came to runs scored. The Yankees covered up many of their sins — and deficiencies — with a few timely long balls and some standout pitching performances from Masahiro Tanaka and James Paxton.

While hindsight is always perfect, because we know who failed and who succeeded, I want to ask an obvious question. Why was our designated hitter doing little more than striking out? It’s clear that our enigmatic catcher Gary Sánchez, who has a talent for crushing balls deep into the night, seems to disappear at big moments.

And, while we’re playing the hindsight game, it seems obvious that closer Aroldis Chapman, who has lost a few miles per hour on his fastball and now relies on an effective slider, should have avoided pitching to José Altuve with two outs, a runner on first and a defensive replacement on deck for Houston.

So, one at a time. Edwin Encarnación was a compelling pickup from Seattle Mariners during the season, offering a few moments of ball-bashing power. Perhaps because of injury, or maybe because he was trying to hit a defining titanic home run, he couldn’t do much of anything in the postseason. The same seems true for the multimillion dollar Giancarlo Stanton.

Given that both can hit huge home runs and are capable of changing the complexion of a low-scoring game, I understand the urge to put them in, but, at some point, if they are not getting it done, why not go with other options? Sure, Cameron Maybin doesn’t hit as many home runs and isn’t as physically imposing. 

If manager Aaron Boone had inserted him into the lineup, would he have taken away the possibility of using Maybin as a late-inning defensive replacement? That’s possible. OK, then, how about using Austin Romine as the designated hitter? Yes, I understand that Boone might also have been saving him to give Sánchez a break in a game where defense takes precedence.

If either of them had become an unconventional designated hitter, would fans be screaming about the panic move if they had failed? Yes, of course, they would. But at least Boone would have been trying something — anything — when he seemed wedded to a script that wasn’t working in a short series.

The same thing holds true for Adam Ottavino. The guy was a great pitcher during the season, but he ran into the postseason twilight zone. It happens. Sit him down and don’t let him affect the outcome of games.

As for Sánchez, he may have hit batting practice pitches into the next county, but that’s irrelevant. He wasn’t getting it done at or behind the plate. Maybe even a single day off would have changed his approach and would have helped. In a short series, managers can’t wait to see if something that’s not working turns around. The team — and its desperate fans — don’t have the luxury of that kind of time.

The question for next year isn’t whether the Yankees will get a starting pitcher who can throw more innings than the present incumbents, or whether Stanton will make a meaningful postseason contribution. The question is: Will Boone buy into the idea of a team game and give other players a chance? After all, the last time the Yankees won the World Series was a decade ago, in 2009.

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Peter Koo. Photo by ©Gina Motisi, 2019/ CSHL

By Daniel Dunaief

We built a process that works, but we don’t know why. That’s what one of the newest additions to Cold Spring Harbor Laboratory hopes to find out.

Researchers have applied artificial intelligence in many areas in biology and health care. These systems are making useful predictions for the tasks they are trained to perform. Artificial intelligence, however, is mostly a hands-off process. After these systems receive training for a particular task, they learn patterns on their own that help them make predictions.

How these machines learn, however, has become as much of a black box as the human brains that created these learning programs in the first place. Deep learning is a way to build hierarchical representations of data, explained Peter Koo, an assistant professor at the Simons Center for Quantitative Biology at CSHL, who studies the way each layer transforms data and the next layer builds upon this in a hierarchical manner.

Koo, who earned his doctorate at Yale University and performed his postdoctoral research at Harvard University, would like to understand exactly what the machines we created are learning and how they are coming up with their conclusions.

“We don’t understand why [these artificial intelligence programs] are making their predictions,” Koo said. “My postdoctoral research and future research will continue this line of work.”

Koo is not only interested in applying deep learning to biological problems to do better, but he’s also hoping to extract out what knowledge these machines learn from the data sets to understand why they are performing better than some of the traditional methods.

“How do we guide black box models to learn biologically meaningful” information? he asked. “If you have a data set and you have a predictive model that predicts the data well, you assume it must have learned something biologically meaningful,” he suggested. “It turns out, that’s not always the case.”

Deep learning can pick up other trends or links in the data that might not be biologically meaningful. In a simplistic example, an artificial intelligence weather system that tracked rain patterns during the spring might conclude, after seven rainy Tuesdays, that it rains on Tuesdays, even if the day of the week and the rain don’t have a causative link.

“If the model is trained with limited data that is not representative, it can easily learn patterns that are correlative in the training data,” Koo said. He tries to combat this in practice by holding out some data, which is called validating data. Scientists use it to evaluate how well the model generalizes to new data.

Koo plans to collaborate with numerous biologists at Cold Spring Harbor Laboratory, as well as other quantitative biologists, like assistant professors Justin Kenney and David McCandlish.

In an email, Kenney explained that the Simons Center is “very interested in moving into this area, which is starting to have a major impact on biology just as it has in the technology industry.”

The quantitative team is interested in high-throughput data sets that link sequence to function, which includes assays for protein binding, gene expression, protein function and a host of others. Koo plans to take a “top down” approach to interpret what the models have learned. The benefit of this perspective is that it doesn’t set any biases in the models.

Deep learning, Koo suggested, is a rebranding of artificial neural networks. Researchers create a network of simple computational units and collectively they become a powerful tool to approximate functions.

A physicist by training, Koo taught himself his expertise in deep learning, Kenney wrote in an email. “He thinks far more deeply about problems than I suspect most researchers in this area do,” he  wrote. Kenney is moving in this area himself as well, because he sees a close connection between the problem of how artificial intelligence algorithms learn to do things and how biological systems mechanistically work.

While plenty of researchers are engaged in the field of artificial intelligence, interpretable deep learning, which is where Koo has decided to make his mark, is a considerably smaller field.

“People don’t trust it yet,” Koo said. “They are black box models and people don’t understand the inner workings of them.” These systems learn some way to relate input function to output predictions, but scientists don’t know what function they have learned.

Koo chose to come to Cold Spring Harbor Laboratory in part because he was impressed with the questions and discussions during the interview process.

Koo, daughter Evie (left) and daughter Yeonu (right) during Halloween last year. Photo by Soohyun Cho

He started his research career in experimental physics. As an undergraduate, he worked in a condensed matter lab of John Clarke at the University of California at Berkeley. He transitioned to genomics, in part because he saw a huge revolution in next-generation sequencing. He hopes to leverage what he has learned to make an impact toward precision medicine. 

Biological researchers were sequencing all kinds of cancers and were trying to make an impact toward precision medicine. “To me, that’s a big draw,” Koo said, “to make contributions here.”

A resident of Jericho, Koo lives with his wife, Soohyun Cho, and their 6-year-old daughter Evie and their 4-year old-daughter Yeonu.

Born and raised in the Los Angeles area, he joined the Army Reserves after high school, attended community college and then transferred to UC Berkeley to get his bachelor’s degree in physics.

As for his decision to join Cold Spring Harbor Laboratory, Koo said he is excited with the opportunity to combine his approach to his work with the depth of research in other areas. 

“Cold Spring Harbor Laboratory is one of those amazing places for biological research,” Koo said. “What brought me here is the quantitative biology program. It’s a pretty new program” that has “incredibly deep thinkers.”

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By Daniel Dunaief

Daniel Dunaief

I like to play Google games, just to see how many results I can get on certain search terms. I know I’ve come up with something incredibly specific when the list is 100 or fewer.

Now, to play my game, I sometimes use quotes to increase the specificity of a particular search. For example, I might be interested in hamburgers or “hamburger helper.” The former brought up 481 million in a recent search and the latter, as you might have guessed, was much lower, at 1.3 million. Please know that the figures I am quoting are never static.

Given the highly public nature of the 45th president, Donald Trump (R), I thought I’d check to see how a man who was once a TV personality did on Google. And, from what I can tell, he is winning the search war.

The words “Donald Trump” netted 520 million results. For someone who appears to enjoy the spotlight, even when people are raging against him, that number is impressive. That’s well above the 141 million for Mickey Mouse and the 60 million for our first president, George Washington. Granted, he has been dead for almost 220 years and Mickey is an animated creature. It is, however, below the 633 million for Brexit.

OK, so let’s compare Trump to, say, the 44th president. While President Barack Obama (D) did better than Washington, he didn’t climb as high as Mickey, getting 109 million results. He was, however, twice as popular in the search engine as his immediate predecessor, President George W. Bush, whose name, complete with the “W.,” brought 54.6 million hits. Ah, but then “Dubya,” as he was called, was higher than President Bill Clinton (D), who netted only 33.8 million results.

So, what does this mean? Maybe it suggests that presidents are on a Google escalator and that the modern reality is that the internet has become the way people search for news about the men who have led our country. The 2020 winner likely stands to become an internet search winner, too.

Assuming that the Google popularity contest is relevant, what does it say about the Democratic presidential candidates? Well, a front-runner and former Vice President Joe Biden brought 107 million results. As an aside, that’s well above the 37.5 million results from the person who holds the office of vice president today, Mike Pence (R).

Back to the Democratic candidates. Elizabeth Warren stands at 47.1 million. That beats Pence, but she’s not running for vice president, at least not yet. Whoops, bad Dan. Bernie Sanders, who ran an impressive campaign in 2016, brings up 70.2 million results, which is much higher than Warren, despite her impressive political career. Kamala Harris has 18.5 million results, with others, like Cory Booker, at 5.6 million.

But, wait, is this a popularity contest? Well, yes and no, right? These candidates need sufficient visibility to attract votes. People also need to be interested in them, right? Does former Democratic presidential candidate Hillary Clinton’s 90.9 million results mean she’s more visible than some of the people running for president? No, it’s a reflection of her close run for the highest office in the land in 2016. That is pretty impressive for someone who wasn’t elected, but is well below singer Taylor Swift’s 415 million.

Perhaps the president in 2020, whether it be the incumbent or a challenger, will immediately see a spike in results, as people around the world type in his or her name each day to find the latest news related to the country and to his or her policies.

As an aside, I couldn’t help wondering how often the current president mocks someone or something. The term “Trump mocks” brought up 747,000 results. By comparison, “Biden mocks” only had 14,700 results. Then again, “Trump applauds” had 82,500 results, compared with “Biden applauds,” which had 3,090. No wonder Trump fatigue has set in for some people: He’s everywhere on the internet.

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From left, Luisa Escobar-Hoyos, Lucia Roa and Ken Shroyer Photo by Cindy Leiton

By Daniel Dunaief

The prognosis and treatment for cancer varies, depending on the severity, stage and type of disease. With pancreatic ductal adenocarcinoma, the treatment options are often limited and the prognosis for most patients by the time doctors make a diagnosis is often bleak.

Researchers at the Renaissance School of Medicine’s Pathology Department at Stony Brook University have been testing for the presence of a protein called keratin 17, or K17, by staining tissue specimens or needle aspiration biopsy specimens. This measures the proportion of tumor cells that have high levels of expression.

This protein is typically active during embryological development or in stem cells, which are a type of cell that can differentiate into a wide range of other cells. It is also active in pancreatic cancer.

Ken Shroyer, department chairman; Luisa Escobar-Hoyos, assistant professor of pathology; and Lucia Roa, assistant professor of pathology recently published a paper in the journal Scientific Reports in which they documented how the level of this protein can indicate the prognosis for patients. K17 above a certain level typically suggests a worse prognosis.

The Stony Brook scientists want to understand why some pancreatic cancers are more aggressive than others, with the hope that they might be able to develop more effective ways to treat the most aggressive form of the disease.

In the recent research, the level of K17 not only indicated the prognosis for the most aggressive form of the disease, but it is also considered a “cause of making the tumors more aggressive,” Escobar-Hoyos added, which confirmed their previously published research and which unpublished data also supports.

Shroyer suggested that this research paper has been a validation of their plan to pursue the development of K17 as a way to differentiate one form of this insidious cancer from another.

While other cancers, such as cervical cancer, have proven quicker and easier to use K17 for its predictive power, the current work reflects the lab’s focus on pancreatic cancer. As such the research is a “great step forward to generate our first pancreatic cancer paper,” Shroyer said. His lab had previously published papers on other biomarkers in pancreatic cancer.

Escobar-Hoyos indicated that she and Shroyer anticipate that K17, which is one of a family of 54 different types of keratins in the human body, likely plays numerous roles in promoting cancer.

Indeed, K17 may promote the invasiveness of these cells, allowing them to spread from the original organ, in this case the pancreas, to other parts of the body. They are testing that concept through ongoing work in their lab.

The researchers believe that K17 may accelerate metastasis, but that line of thinking is “still at a relatively early stage,” Escobar-Hoyos said.

This protein may also change the metabolism of the cell. They believe K17 blocks the uptake of certain drugs by enhancing specific metabolic pathways. 

Additionally, K17 causes the degradation of p27, which is a tumor suppressor that controls cell division.

The researchers used two different ways to monitor the levels of protein, through mRNA analysis and through immunohistochemical localization. In the latter case, that involved staining the cells to look for the presence of the protein.

Roa, who is the first author on the paper, stained the slides and worked with Shroyer to score them.

The assistant professor, who came to Long Island with her daughter Laura who earned her bachelor’s degree and master’s in public policy at SBU, had been a pathologist and medical doctor when she lived in Colombia. She learned the IHC staining technique at Yale University just after she graduated from medical school and worked for six years as a postdoctoral fellow on several projects using IHC.

Roa is thrilled that she’s a part of a supportive team that could help develop techniques to improve patient diagnosis and care.

“We care deeply about developing a tool that will help us to treat patients and we value working together to accomplish this,” Roa explained in an email.

At this point, Shroyer and his team have identified key factors that cause K17 to be overexpressed. They are pursuing this line of research in the lab.

“We think K17 expression is dictated by something different than genetic status,” said Escobar-Hoyos. “This is speculation, but we think it might be triggered based on a patient’s immunity.”

After this study, the pathology team is looking to validate their results through different cohorts of patients. They are working with the Pancreatic Cancer Action Network and their scientific collaborators at Perthera Inc. to process tissue sections from these cases for K17 staining in their lab.

They are also at the early stages in the development of a collaboration with investigators at MD Anderson Cancer Center.

“If we can validate that K17 IHC testing is able to predict a response to the standard of care, then we’ll have permission to start a prospective analysis linked to a clinical trial,” Shroyer said.

Shroyer’s team is trying to understand how K17 becomes activated, what happens when they block that activation, and how it impacts the survival and tumor growth in animal models of pancreatic cancer.

In collaborations with other researchers, they are exploring how K17 impacts the therapeutic vulnerability of pancreatic cancer to over 2,000 FDA-approved compounds.

“There are a discrete list of compounds that are able to kill K17 positive cells,” Shroyer said. He is aiming to start phase 0 trials to validate the molecular model. If the data is sufficiently convincing, they can apply to the FDA to begin phase 1 trials.

He hopes this study is the first of many steps the lab will take in providing clues about how to diagnose and treat pancreatic cancer, which has been an intractable disease for researchers and doctors.

“This paper helps establish and confirm that K17 is an important and promising prognostic biomarker in pancreatic cancer,” Shroyer said. “For us, this is foundational for all the subsequent mechanistic studies that are in progress to understand how K17 drives cancer aggression.”

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By Daniel Dunaief

Daniel Dunaief

I speak with a police officer near my son’s school regularly. She steps into four lanes of frantic morning commuting traffic to allow people to maneuver into and out of a school parking lot.

She offers a pleasant, “Good morning,” to people who roll down their windows or who walk past her. As she steps carefully into a heavily trafficked street, she makes eye contact with drivers.

She waves to the waiting parents to make their turns and rejoin the flow of traffic to work or to their next morning destination. She sends them off from school with a pleasant, “Have a great day,” as they drive around her.

Recently, I pulled up to the stop sign and saw the officer holding her stomach.

“What’s happening?” I asked.

“I just can’t stop laughing,” she said. “I see the same crazies every day. I’m used to them. There’s this guy who drives a pickup truck and he cusses at me every time he passes. I’m not sure why.”

“Is that funny?” I asked.

“No, today, a woman looked right at me, clapped, gave me the thumbs up and raised her fist. She seemed so happy that I was here.”

“That’s great,” I said.

“Yeah, she made my day,” the officer said, again holding her stomach. “That was just
so funny.”

This police officer spends her day looking in car windows, hoping people stop instead of running her over or creating traffic hazards for children or their parents near schools. And yet, this driver made her happy by sharing an effusive and appreciative series of simple gestures.

The movements the woman made are the kinds of displays superstar athletes see every time they step on a sports field or tennis court. These expressions of appreciation, gratitude and admiration are so common that many of the players block out the sounds so they can focus on the game.

But for this officer, the show of support was a welcome sight.

A day before, a friend told me that he and his daughter pulled into a parking lot, where a parking attendant asked for $3. When he handed out the money, his daughter leaned across him and thanked the attendant.

The attendant smiled and directed them to a spot nearby.

“What are you thanking him for?” my friend asked. “What did he do?”

“He’s doing his job and I appreciate it,” his daughter said. “Why can’t you appreciate it?”

“He’s taking my money,” the friend reasoned. 

“Yes, and you’re getting a place to park,” she said.

My friend recognized the value of the words. Besides, even if it didn’t make the attendant’s day, it didn’t cost anything and it may have helped the car park collector feel like someone cared that a good job was being done.

In that same vein, I’d like to thank you for reading this column today and any other time you take the time to read it. I know you could be doing numerous other tasks and I appreciate the opportunity to share words, thoughts or experiences with you. 

I realize you don’t always agree with me. Maybe climate change isn’t top of your mind or you have perfect children who never once frustrate and amuse you, or your dog is so well trained that it never jumps up on anyone or consumes a plate full of warm cookies. But I appreciate the chance to connect with you.

Maybe today, tomorrow or next week, you can also pass along an appreciative gesture. Who knows? You might make the day of a police officer, a baker, a mail carrier or a dog walker.

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Dr. Minsig Choi and Paul Bingham. Photo from Stony Brook Medicine

By Daniel Dunaief

The Stony Brook Cancer Center is seeking patients with pancreatic cancer for a phase 3 drug trial of a treatment developed by a husband and wife team at SBU.

Dr. Minsig Choi. Photo from Stony Brook Medicine

Led by Minsig Choi, the principal investigator of the clinical trial and a medical oncologist at Stony Brook Cancer Center’s gastroenterology team, the study is part of a multicenter effort to test whether a drug known as CPI-613, or devimistat, can extend the lives of people battling against a form of cancer that often has a survival rate of around 8 percent five years after its discovery.

Paul Bingham. Photo from Stony Brook Medicine

Patients at Stony Brook will either receive the conventional treatment of FOLFIRINOX, or a combination of a FOLFIRINOX and CPI-613. An earlier study demonstrated a median survival of 20 months with the combination of the two drugs, compared with 11 months with just the standard chemotherapy.

“Pancreatic cancer is such a bad disease,” Choi said. “The overall survival is usually less than a year and life expectancy is very limited.”

Choi said the company that is developing the treatment, Rafael Pharmaceuticals, wanted Stony Brook to be a part of the larger phase 3 study because the drug was developed at the university. Indeed, Stony Brook is the only site on Long Island that is offering this treatment to patients who meet the requirements for the study.

People who have received treatment either from Stony Brook or at other facilities are ineligible to be a part of the current trial, Choi said. Additionally, patients with other conditions, such as cardiac or lung issues, would be excluded.

Additionally, the current study is only for “advanced patients with metastatic” pancreatic cancer, he said. People who have earlier forms of this cancer usually receive surgery or other therapies.

“When you’re testing new drugs, you want to start in a more advanced” clinical condition, he added.

Choi said patients who weren’t a part of the study, however, would still have other medical options.

Zuzana Zachar. Photo from Stony Brook Medicine

“The clinical trial is not the only way to treat” pancreatic cancer, he said. These other treatments would include chemotherapy options, palliative care, radiation therapy and other supportive services through social workers.

Choi anticipates that the current study, which his mentor Philip A. Philip, a professor in the Department of Oncology at the Barbara Ann Karmanos Cancer Institute in Detroit is leading, would likely provide preliminary results in the next 18 to 24 months.

If the early results prove especially effective, the drug may receive a fast-track designation at the Food and Drug Administration. That, however, depends on the response rate and the way patients tolerate the treatment.

At this point, Choi anticipates that most of the side effects will be related to the use of chemotherapy, which causes fatigue and weakness. The CPI-613, at least in preliminary studies, has been “pretty well tolerated,” although it, like other drug regimes, can cause upset stomachs, diarrhea and nausea, he said.

Doctors and researchers cautioned that cancer remains a problematic disease and that other drugs to treat forms of cancer have failed when they reach this final stage before FDA approval, in part because cancer can and often does develop ways to work around efforts to eradicate it.

Still, the FDA wouldn’t have approved the use of this drug in this trial unless the earlier studies had shown positive results. Prior to this broader clinical effort, patients who used CPI-613 in combination with FOLFIRINOX had a tumor response rate of 61 percent, compared with about half that rate without the additional treatment.

Paul Bingham, an associate professor in the Department of Biochemistry and Cell Biology at Stony Brook University, and his wife Zuzana Zachar, a research assistant professor and director of Master in Teaching Biology Program at the Institute for STEM Education at Stony Brook, originally invented and discovered the family of drugs that includes CPI-613.

Bingham and Zachar, who are consultants to Rafael Pharmaceuticals, “provide basic scientific support” in connection with this phase 3 trial. “When the FDA asks questions, sometimes it requires us to do basic science” to offer replies, he said.

Zachar and Bingham developed this drug because they anticipated that attacking cancer cell’s metabolism could lead to an effective treatment. Cancer requires considerable energy to continue on its deadly course. This drug, which is a lipoate analog and is an enzyme cofactor in several central processes in metabolism, tricks the disease into believing that it has sufficient energy. Interrupting this energy feedback mechanism causes the cancer cell to starve to death. 

While other cells use some of the same energy feedback pathways, they don’t have the same energy demands and the introduction of the drug, which has tumor-specific effects, is rarely fatal for those cells.

The lipoate analog is a “stable version of the normally transient intermediary that lies to the regulatory systems, which causes them to shut down the metabolism of cancer cells,” Bingham said. These cells “run out of energy.”

Zachar said the process of understanding how CPI-613 could become an effective treatment occurred over the course of years and developed through an “accretion of data that starts to fill in a picture and eventually you get enough information to say that it could be” a candidate to help patients. The process is more “incremental than instantaneous.”

Bingham and Zachar are working on a series of additional research papers that reflect the way different tumors and tumor types have different sensitivities to CPI-613. They expect to publish at least one new paper this year and several more next year.

The researchers who developed this drug have had some contact with patients through the process. While they are not doctors, they are grateful that the work they’ve done has “extended and improved people’s lives,” Bingham said, and they are “grateful for that opportunity.”

Zachar added that she is “thrilled that we’ve been able to help.” She appreciates the contribution the patients make to this research because they “stepped to the line and took the risk to try this drug.”

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Stock photo
Daniel Dunaief

We think we know our kids, but really the converse is true.

My son recently told me that he thinks I’m angry every time I swim laps in a pool. At first, I dismissed the observation because swimming brings me peace.

And then I thought about my junior year of high school, when I joined my one and only swim team.

I loved the water, I had a few friends on the team and I was determined to do something different when each day in school felt like a bad version of “Groundhog Day,” long before the Bill Murray film arrived in theaters.

I had several shortcomings. For starters, I didn’t know how to do a flip turn. To the experienced swimmer, that’s as laughable as asking a NASCAR driver how to change gears or a baseball player which end of the bat to hold. It’s a basic skill. I’d approach the wall, gasping for air, roll to my right and kick hard.

Most of the time, I’d slam my foot into the lane marker and, on occasion would kick the poor swimmer in lane 5. I swam in lane 6, which was where swimmers who needed life jackets trained. The best swimmers occupied lane 1. They never seemed to need a breath, had hydrodynamic bodies that made them look like torpedoes and seemed slightly bored after an exhausting practice.

Oh, and they also wore Speedo bathing suits well. For someone accustomed to the boxing trunk bathing suits that I still wear today, Speedos seemed way too small. Besides, I’m not sure the small, colorful lightweight suits allowed me to shave even a tenth of a second off my barge-floating-downstream speed.

Each practice, the coach would tell us to swim 20 laps back and forth as a warm-up. By the end of the warm-up, which I never finished, we started practice. At that point, I was leaning hard on the wall, wondering whether I should climb out of the pool and grab some French fries.

When we dove off the blocks at the start of the race, I must have entered the water at the wrong angle. My goggles scraped down my nose and landed in front of my mouth, which made it impossible to see or breathe. Flopping blindly, I’d zigzag in slow motion across the pool.

Each practice completely drained me. My exhausted arms pulled through the water, splashing where others were gliding. My legs slapped at the water, instead of serving as propellers. And yet, something about the incredible energy required to survive each practice helped me, both mentally and physically.

I’m sure I lost weight. After all, such inefficient swimming burns off considerably more calories than floating effortlessly hither and yon. More importantly, though, I worked out everything that bothered me in my head as I listened to the gurgling noises my mouth made while I wiggled back and forth. Each lap, I replayed conversations that went awry, standardized tests that were like electroshock therapy and the missed social opportunities.

Gnashing my teeth, I worked out frustrations that built up during the day or the week. The herculean effort either removed toxins or prevented them from cluttering my brain. Sitting in my room at home after practice, I felt more at peace than I had at any point during the day.

But what my son must have perceived as I do laps today are the habits I formed during that winter season. My body instantly remembers how to use swimming to release tension. He may see the residual physical manifestations of the cauldron of emotions that I carried back and forth across that icy pool. And, hey, maybe I’d look like a happier swimmer if I ever learned how to do a flip turn.

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